PurposeTo measure levels of high-mobility group box −1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice.MethodsVitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting.ResultsHMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1β was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice.ConclusionsSubclinical chronic inflammation might contribute to the progression of PDR.

Purpose Stem cell factor (SCF)/c‐kit signaling promotes recruitment of endothelial progenitor cells and contributes to ischemia‐induced new vessel formation. We investigated the expression of the components of this pathway including c‐kit, SCF, granulocyte colony‐stimulating factor (G‐CSF), endothelial nitric oxide synthase (eNOS), and the chemokine receptor CXCR4 in proliferative diabetic retinopathy (PDR) epiretinal membranes. Methods Membranes from 8 patients with active PDR and 12 patients with inactive PDR were studied by immunohistochemistry. Results Blood vessels expressed c‐kit, SCF, G‐CSF, eNOS, and CXCR4 in 18, 15, 19, 20 and 20 out of 20 membranes, respectively. Significant correlations were detected between number of blood vessels expressing CD34 and number of blood vessels expressing SCF (r=0.463; p=0.04), G‐CSF (r=0.87; p<0.001), eNOS (r=0.864; p<0.001), and CXCR4 (r=0.864; p<0.001). Stromal cells expressed c‐kit, SCF, eNOS, and CXCR4 in 19, 15, 20, and 20 membranes, respectively. The numbers of blood vessels expressing CD34 (p=0.005), c‐kit (p=0.03), G‐CSF (p=0.007), eNOS (p=0.001), and CXCR4 (p=0.018), and stromal cells expressing c‐kit (p=0.013), SCF (p<0.001), eNOS (p=0.048), and CXCR4 (p=0.003) were significantly higher in active membranes than in inactive membranes. Conclusion SCF/c‐kit signaling might contribute to neovascularization in PDR.

Purpose: To determine prognostic factors in patients with Vogt‐Koyanagi‐Harada (VKH) disease who were treated with high‐dose corticosteroids. Methods: Analysis of 87 patients (174 eyes). Results: Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton‐fat keratic precipitates, anterior chamber reaction of 2+ or more, iris nodules and posterior synechiae, less exudative retinal detachment at presentation, more complications during the follow‐up period and a worse visual outcome. The use of immunomodulatory therapy as first line therapy significantly reduced the development of complications in the whole study group and in initial‐onset acute group and improved visual outcome in the whole study group. In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 and age older than 16 years was significantly associated with the development of complications. Conclusions: Chronic recurrent VKH disease is significantly associated with more severe inflammation at presentation and more complications. Use of immunomodulatory therapy improves clinical outcome.

Abstract. Purpose:  To study the effectiveness of mycophenolate mofetil (MMF) as first‐line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt–Koyanagi–Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy. Methods:  This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease. Results:  The mean follow‐up period was 27.0 ± 11.1 months (range 16–54 months). Corticosteroid‐sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3–7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3–41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed ‘sunset glow fundus’. Conclusions:  Addition of MMF as first‐line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.

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The diagnostic work-up, investigational tests, and differential diagnosis to confirm or reject the diagnosis of VKH as well as the management of the case will be described by the experts.

To study the effectiveness of mycophenolate mofetil (MMF) combined with systemic corticosteroids in acute uveitis associated with Vogt‐Koyanagi‐Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy. Nineteen patients (38 eyes) were studied prospectively. Mean follow‐up period was 27.011.1 months. Corticosteroid‐sparing effect was achieved in all patients. Mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.11.2 months. Ten (53%) patients discontinued treatment without relapse of inflammation. Mean time observed off of treatment was 17.311.9 months. Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p<0.001). Recurrent inflammation of 3 times was reduced significantly (p=0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group ( 18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared to the corticosteroid + MMF group (8%) (p<0.001). None of the eyes in the corticosteroid + MMF group developed “sunset glow fundus”.

Purpose Role of vasculogenesis, recruitment and differentiation of circulating bone marrow‐derived endothelial precursor cells into mature endothelium, in proliferative diabetic retinopathy (PDR) remains undefined. We investigated the presence of bone marrow‐derived endothelial precursor cells and the expression of the chemotactic pathway SDF‐1/CXCL12?CXCR4 in PDR epiretinal membranes. Methods Membranes from 8 patients with active PDR and 9 patients with inactive PDR were studied by immunohistochemistry using antibodies against CD133, vascular endothelial growth factor receptor‐2 (VEGFR‐2), CD14, SDF‐1 and CXCR4. Results Blood vessels expressed CD133, VEGFR‐2, CD14, SDF‐1 and CXCR4 in 10, 10, 10, 7 and 7 out of 17 membranes, respectively. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing CD133 (rs=0.646; p=0.005), VEGFR‐2 (rs=0.704; p=0.002), CD14 (rs=0.564; p=0.018), and SDF‐1 (rs=0.577; p=0.015). Stromal cells in close association with blood vessels expressed CD133, VEGFR‐2, CD14, and CXCR4 in 10, 12, 13, and 14 membranes, respectively. Number of blood vessels expressing CD133 (p=0.013), VEGFR‐2 (p=0.005), CD14 (p=0.008) and SDF‐1 (p=0.005), and stromal cells expressing CD133 (p=0.003), VEGFR‐2 (p=0.013) and CD14 (p=0.002) was significantly higher in active membranes than in inactive membranes. Conclusion Bone marrow‐derived CD133+ endothelial progenitor cells and CD14+ monocytes may contribute to vasculogenesis in PDR.